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Science 31 July 1992:
Vol. 257. no. 5070, pp. 674 - 678
DOI: 10.1126/science.1323141
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Articles

Science, Vol 257, Issue 5070, 674-678
Copyright © 1992 by American Association for the Advancement of Science

articles

Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1

IA Drummond, SL Madden, P Rohwer-Nutter, GI Bell, VP Sukhatme, and FJ Rauscher 3rd

Howard Hughes Medical Institute, University of Chicago, IL 60637.

The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.


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J. Biol. Chem. 272, 32836-32846
   Abstract »    Full Text »    PDF »
PAX 8 Regulates Human WT1 Transcription through a Novel DNA Binding Site.
G. C. Fraizer, R. Shimamura, X. Zhang, and G. F. Saunders (1997)
J. Biol. Chem. 272, 30678-30687
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P. Nair, S. Muthukkumar, S. F. Sells, S.-S. Han, V. P. Sukhatme, and V. M. Rangnekar (1997)
J. Biol. Chem. 272, 20131-20138
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High Levels of Wilms' Tumor Gene (wt1) mRNA in Acute Myeloid Leukemias Are Associated With a Worse Long-Term Outcome.
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Blood 90, 1217-1225
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Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer.
G. B. Silberstein, K. Van Horn, P. Strickland, C. T. Roberts Jr., and C. W. Daniel (1997)
PNAS 94, 8132-8137
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G. Dong, R. Rajah, T. Vu, A. R. Hoffman, R. G. Rosenfeld, C. T. Roberts Jr., D. M. Peehl, and P. Cohen (1997)
J. Clin. Endocrinol. Metab. 82, 2198-2203
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Developmental regulation and the role of insulin and insulin receptor in metanephrogenesis.
Z. Z. Liu, A. Kumar, K. Ota, E. I. Wallner, and Y. S. Kanwar (1997)
PNAS 94, 6758-6763
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Design of TATA box-binding protein/zinc finger fusions for targeted regulation of gene expression.
J.-S. Kim, J. Kim, K. L. Cepek, P. A. Sharp, and C. O. Pabo (1997)
PNAS 94, 3616-3620
   Abstract »    Full Text »    PDF »
Sp1 Is a Critical Regulator of the Wilms' tumor-1 Gene.
H. T. Cohen, S. A. Bossone, G. Zhu, G. A. McDonald, and V. P. Sukhatme (1997)
J. Biol. Chem. 272, 2901-2913
   Abstract »    Full Text »    PDF »
Increased Expression of the Insulin-like Growth Factor-II Gene in Wilms' Tumor Is Not Dependent on Loss of Genomic Imprinting or Loss of Heterozygosity.
W.-H. Wang, J.-X. Duan, T. H. Vu, and A. R. Hoffman (1996)
J. Biol. Chem. 271, 27863-27870
   Abstract »    Full Text »    PDF »
Molecular Cloning of the cDNA and Chromosome Localization of the Gene for Human Ubiquitin-conjugating Enzyme 9.
Z.-Y. Wang, Q.-Q. Qiu, W. Seufert, T. Taguchi, J. R. Testa, S. A. Whitmore, D. F. Callen, D. Welsh, T. Shenk, and T. F. Deuel (1996)
J. Biol. Chem. 271, 24811-24816
   Abstract »    Full Text »    PDF »
Mapping of Pax-2 Transcription Activation Domains.
MarkS. Lechner and GregoryR. Dressler (1996)
J. Biol. Chem. 271, 21088-21093
   Abstract »    Full Text »    PDF »
Egr-1 Activates Basic Fibroblast Growth Factor Transcription. MECHANISTIC IMPLICATIONS FOR ASTROCYTE PROLIFERATION.
E. Biesiada, M. Razandi, and E. R. Levin (1996)
J. Biol. Chem. 271, 18576-18581
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CCAAT Displacement Protein Competes with Multiple Transcriptional Activators for Binding to Four Sites in the Proximal gp91phox Promoter.
W. Luo and D. G. Skalnik (1996)
J. Biol. Chem. 271, 18203-18210
   Abstract »    Full Text »    PDF »
The KRAB Zinc Finger Gene ZNF74 Encodes an RNA-binding Protein Tightly Associated with the Nuclear Matrix.
B. Grondin, M. Bazinet, and M. Aubry (1996)
J. Biol. Chem. 271, 15458-15467
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Differential Function of Wilms' Tumor Gene WT1 Splice Isoforms in Transcriptional Regulation.
S. M. Hewitt, G. C. Fraizer, Y.-J. Wu, F. J. Rauscher III, and G. F. Saunders (1996)
J. Biol. Chem. 271, 8588-8592
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A Non-AUG Translational Initiation Event Generates Novel WT1 Isoforms.
W. Bruening and J. Pelletier (1996)
J. Biol. Chem. 271, 8646-8654
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Alterations in the Promoter-specific Imprinting of the Insulin-like Growth Factor-II Gene in Wilms' Tumor.
T. H. Vu and A. R. Hoffman (1996)
J. Biol. Chem. 271, 9014-9023
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Suppression of Interleukin-1beta-converting Enzyme-mediated Cell Death by Insulin-like Growth Factor.
Y.-K. Jung, M. Miura, and J. Yuan (1996)
J. Biol. Chem. 271, 5112-5117
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Mechanisms Identified in the Transcriptional Control of Epithelial Gene Expression.
G. Hennig, O. Löwrick, W. Birchmeier, and Jür. Behrens (1996)
J. Biol. Chem. 271, 595-602
   Abstract »    Full Text »    PDF »
The Transcriptional Effect of WT1 Is Modulated by Choice of Expression Vector.
J. C. Reddy, S. Hosono, and J. D. Licht (1995)
J. Biol. Chem. 270, 29976-29982
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Repression of the c-myb Gene by WT1 Protein in T and B Cell Lines.
S. McCann, J. Sullivan, J. Guerra, M. Arcinas, and L. M. Boxer (1995)
J. Biol. Chem. 270, 23785-23789
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Isolation and Characterization of a Novel Zinc-finger Protein with Transcriptional Repressor Activity.
A. J. Williams, L. M. Khachigian, T. Shows, and T. Collins (1995)
J. Biol. Chem. 270, 22143-22152
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The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis..
S Maheswaran, C Englert, P Bennett, G Heinrich, and D A Haber (1995)
Genes & Dev. 9, 2143-2156
   Abstract »    PDF »
Transcriptional Silencer of the Wilms' Tumor Gene WT1 Contains an Alu Repeat.
S. M. Hewitt, G. C. Fraizer, and G. F. Saunders (1995)
J. Biol. Chem. 270, 17908-17912
   Abstract »    Full Text »    PDF »
WT1-mediated Transcriptional Activation Is Inhibited by Dominant Negative Mutant Proteins.
J. C. Reddy, J. C. Morris, J. Wang, M. A. English, D. A. Haber, Y. Shi, and J. D. Licht (1995)
J. Biol. Chem. 270, 10878-10884
   Abstract »    Full Text »    PDF »
Repression of Pax-2 by WT1 during normal kidney development.
G Ryan, V Steele-Perkins, J. Morris, F. Rauscher, and G. Dressler (1995)
Development 121, 867-875
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Novel Oncogenic Mutations in the WT1 Wilms' Tumor Suppressor Gene: A t(11;22) Fuses the Ewing's Sarcoma Gene, EWS1, to WT1 in Desmoplastic Small Round Cell Tumor.
F.J. Rauscher III, L.E. Benjamin, W.J. Fredericks, and J.F. Morris (1994)
Cold Spring Harb Symp Quant Biol 59, 137-146
   Abstract »    PDF »
Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues.
S. Mundlos, J. Pelletier, A. Darveau, M. Bachmann, A. Winterpacht, and B. Zabel (1993)
Development 119, 1329-1341
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Identification of Connective Tissue Growth Factor as a Target of WT1 Transcriptional Regulation.
P. Stanhope-Baker and B. R. G. Williams (2000)
J. Biol. Chem. 275, 38139-38150
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EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis.
J. Svaren, T. Ehrig, S. A. Abdulkadir, M. U. Ehrengruber, M. A. Watson, and J. Milbrandt (2000)
J. Biol. Chem. 275, 38524-38531
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Identification of a Novel Cis Element Required for Cell Density-dependent Down-regulation of Insulin-like Growth Factor-2 P3 Promoter Activity in CaCo2 Cells.
B. Dai, H. Wu, E. Holthuizen, and P. Singh (2001)
J. Biol. Chem. 276, 6937-6944
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Ionizing Radiation Down-regulates p53 Protein in Primary Egr-1-/- Mouse Embryonic Fibroblast Cells Causing Enhanced Resistance to Apoptosis.
A. Das, D. Chendil, S. Dey, M. Mohiuddin, M. Mohiuddin, J. Milbrandt, V. M. Rangnekar, and M. M. Ahmed (2001)
J. Biol. Chem. 276, 3279-3286
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W. Wang, S. B. Lee, R. Palmer, L. W. Ellisen, and D. A. Haber (2001)
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